Effects of acute glutathione depletion induced by L-buthionine-(S,R)-sulfoximine on rat liver glucose-6-phosphatase activity.
The effect of acute glutathione (GSH) depletion induced by GSH-depleting agent L-buthionine-(S,R)-sulfoximine (BSO) on hepatic microsomal glucose-6-phosphatase (G6Pase) activity in male Wistar rats was investigated. Liver GSH evaluated in high-performance liquid chromatography after administration of 4 mmol.Kg-1 BSO i.p. was decreased by 19% and 50% at the time-points of 1.5 h and 3 h, respectively. In these conditions, a significant decrease in Vmax and an increasing trend in K(m) of hepatic G6Pase activity were observed, especially in 3 h BSO-rats. Alterations in kinetic parameters of G6Pase were calculated in both intact and detergent-treated microsomes, using glucose-6-phosphate and pyrophosphate as substrate. A little increase in thiobarbituric acid-reactive substances and a limited decrease in 5,5'-dithiobis(2-nitrobenzoate)-reactive protein thiols were also noted. The results of this study show that acute GSH depletion induced by BSO is able to affect hepatic microsomal G6Pase activity. A possible explanation to account for the effect of BSO-induced GSH depletion on hepatic G6Pase system is discussed.
Santori
G
G
Institute of General Pathology, University of Genoa, Italy.
Domenicotti
C
C
Bellocchio
A
A
Pronzato
M A
MA
Marinari
U M
UM
Poli
G
G
Cottalasso
D
D
D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D005978:Glutathione / Q000502:physiology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D019328:Buthionine Sulfoximine; D005952:Glucose-6-Phosphatase; D005978:Glutathione